Ovarian cysts and tumors: Pathology review

Chapters:

Watch video only

Case Study0:00–1:24

65-year-old Rebecca presents to the clinic with several months of abdominal discomfort, bloating, and a change in bowel habits.
Her past medical history is significant for endometriosis. Menarche was at age 10 and menopause at age 57.
She has never been pregnant. On physical examination, a slightly painful nodule is palpated around the umbilicus.
Transvaginal ultrasound showed a large, irregular cyst with heterogeneous fluid in her right ovary. Later that day, 6-year-old Gloriana is brought to the office by her mother, who is worried that her daughter is more “womanly” and taller than the other girls her age.
Over the last few months, she has also occasionally complained of vague abdominal pain. Physical examination reveals coarse pubic hair and significant breast enlargement.
The child’s height is also in the 96th percentile. Laboratory studies also showed increased inhibin b levels.Based on the initial presentation, Rebecca and Gloriana’s symptoms are caused by some form of ovarian mass.
Broadly speaking, ovarian masses include ovarian cysts and tumors. Starting with ovarian cysts, these are fluid-filled sacs on or in the ovaries and can be classified into simple and complex cysts.
Simple cysts are generally small, they contain a clear serous liquid, and have a smooth internal lining. The classic example is a follicular cyst which is a dominant follicle that fails to rupture before ovulation and keeps growing.

Ovarian Cyst1:24–3:44

This can happen, if say, the normal surge of LH that causes ovulation just doesn’t happen during a given menstrual cycle.
In fact, follicular cysts are the most common type of ovarian mass in young individuals. For your test, remember that if you encounter multiple follicular cysts, they are usually associated with polycystic ovary syndrome, or PCOS.
This is caused by a dysfunction in the hypothalamic-pituitary-ovarian axis that causes chronic anovulation, which may lead to amenorrhea, or absent menstruation, and excess androgen production, which may lead to hirsutism.
Another type of simple cysts are the corpus luteum cysts. Normally, after ovulation, the follicle remnants become the corpus luteum, which regresses during the luteal phase.
If instead of regressing, the corpus luteum continues to grow, then the arteries nourishing it can rupture and hemorrhage into the cyst.
So a high-yield fact to know is that corpus luteum cysts are also called hemorrhagic cysts. The last kind of simple cysts are theca lutein cysts.
These are caused by overstimulation by human chorionic gonadotropin, or hCG, a hormone that’s produced by the placenta, so they’re only seen in pregnancy.
For your test, keep in mind that since hCG stimulates growth of the follicular theca cells and resting follicles can be found on both ovaries, these cysts are usually bilateral.
Another important thing is that theca lutein cysts are much more likely to develop when there’s more hCG than usual, so the scenario will usually include multiple fetuses, or gestational trophoblastic disease, like hydatidiform mole, or choriocarcinoma.
Ok, now, the second category of cysts are complex cysts. These are generally large, have irregular borders, internal septations creating a multilocular appearance and the fluid inside these cysts tends to be heterogeneous, meaning there’s something other than fluid inside it.
In many cases, a complex cyst could be part of an ovarian tumor.Speaking of ovarian tumors, they can be divided into three categories: epithelial ovarian tumors, which derive from the surface epithelium of the ovary, germ cell tumors, which derive from primordial germ cells which are the cells that can give rise to all other tissues and organs, and sex cord-stromal tumors, which derive from sex cord-stromal cells that originate from the connective tissue of the ovary.

Ovarian Tumors3:44–6:31

For your exams, remember that epithelial tumors account for over seventy percent of all ovarian tumors. The other thirty percent comes from germ cell and sex cord-stromal tumors.
Epithelial ovarian tumors can then be subdivided into four types: serous, mucinous, endometrioid and transitional. Serous tumors are usually cystic and full of watery fluid.
Mucinous-type tumors are similar to the serous type, but they’re full of a mucus-like fluid, which is where they get their name.
Both serous and mucinous tumors can be benign, malignant, or borderline, meaning that they have a mix of benign and malignant characteristics.The benign type is called serous or mucinous cystadenoma.
Cystadenomas are usually a single cyst lined with simple cuboidal and columnar cells. On your test, they most commonly arise in premenopausal women who are between thirty and forty years old.
What sets them apart is that serous cystadenomas, which are the most common type of ovarian cyst, tend to be bilateral and are lined with fallopian tube-like epithelium.
On the other hand, only five to ten percent of mucinous cystadenomas are bilateral, and they are lined with mucous secreting epithelium.The malignant type is called serous or mucinous cystadenocarcinoma.
Cystadenocarcinomas have a thick, shaggy lining due to inflammation, edema and overcrowding of the epithelial cells. They are also more common in postmenopausal women.
The serous type, is the most common malignant ovarian neoplasm and they tend to be bilateral. Another high-yield fact to remember is that serous cystadenocarcinomas contain psammoma bodies which are circular plaques of calcium deposits around necrotic or dead cells.
On the other hand, an important clue to the mucinous type is that it can cause pseudomyxoma peritonei, pseudo meaning false, myxoma meaning mucinous tumor, and peritonei telling us its location.
So the mucinous material can leak from the ovary into the peritoneum, resulting in metastasis to the appendix or other parts of the GI tract.Finally, there is a borderline type of both serous and mucinous tumors and it has a mix of characteristics from both benign and malignant types.
The one thing to keep in mind here is that it usually has a better outcome than the malignant type since it is not as likely to metastasize.So then we’ve got tumors from endometrial cells, which are called endometriomas.

Endometriomas6:31–9:29

These are benign cysts within the ovary that occur in endometriosis, which is when endometrial tissue from the uterus grows on the ovary.
Because they’re functionally the same as the endometrial tissue inside the uterus, endometriomas respond to hormones just like the uterus would.
And because of this, endometriomas tend to bleed within the cyst cavity during menstruation, and over time, they fill up with old blood that turns a dark brown color.
Hence examiners love to call them “chocolate cysts”. If these cysts get too large, they can rupture and spill their “chocolate-like” contents inside the peritoneal cavity.
Another commonly tested fact is that there’s a very rare subclass of endometriomas, the endometrioid tumor, which is malignant and composed of endometrial-like glands.
The last type of epithelial tumors come from transitional cells, and these are better known as Brenner tumors. They are benign and made up of bladder like tissue which gives them a pale yellow tan color.
A high-yield fact here is that under the microscope, the cell nuclei are “coffee bean shaped”. In rare cases they can transform into squamous cell carcinoma.
Alright now that we’ve looked at the epithelial tumors, let’s shift gears and go over the germ cell tumors. These are the second most common type, accounting for about fifteen percent of all ovarian tumors.
They can be divided into four subtypes classified by the type of tissue produced by the germ cell, which are fetal, oocyte, yolk sac, and placental tissue.Starting with tumors from fetal tissue, these are called teratomas and are divided into two types.
The first is mature cystic teratoma, also known as dermoid cyst, that has fully developed tissue inside, like skin, hair, nails etc.
These are actually the most common ovarian tumors in females between ten and thirty years old and are bilateral in ten percent of cases.
What’s important is that they tend to be benign. This is unlike mature testicular teratomas in male adults, which tend to be malignant.
However, rarely, they can undergo malignant transformation into squamous cell carcinoma. A special, high-yield type of mature cystic teratoma that only contains thyroid tissue is called a struma ovarii.
These tumors can secrete T3 and T4, leading to hyperthyroidism. So if a question asks about a female with hyperthyroidism, normal thyroid physical examination, low TSH, and an ovarian mass, think of struma ovarii.The other type is immature teratoma which has undifferentiated fetal tissue, and this is most commonly neuroectoderm, the embryonic precursor to neural tissue.
For your exams, it’s important to know that it tends to be malignant and very aggressive, meaning they tend to be invasive.
They typically present quite early, before the age of twenty.Next, tumors from oocyte tissue are called dysgerminomas, and are the most common malignant type of germ cell tumor.

Germ Cell Tumor9:29–12:08

They are most common in adolescents. For your exams, remember that on microscopic examination, the tumor cells are large with central nuclei surrounded by clear cytoplasm.
A key word for that is a “fried-egg appearance”. Another high-yield thing to know is that this is the ovarian analogue of testicular seminoma.
Lactate dehydrogenase or LDH as well as human chorionic gonadotropin or hCG are both markers for this tumor.The third type of germ cell tumor comes from the yolk sac and it’s called endodermal sinus tumor.
Endodermal sinus tumors are malignant and aggressive. What’s high-yield here is that these are the most common germ cell tumor in children.
So, if a test question is about a child, especially if they are younger than 3 years old, with an ovarian mass, think of yolk sac tumor at the top of your differentials.
Another key thing to keep in mind is that, on gross examination, they typically form a yellow hemorrhagic mass, while under the microscope we can see glomeruloid structures or Schiller-Duval bodies.
These are rings of malignant cells around the central blood vessel. Lab tests classically show elevated α-fetoprotein or AFP levels.Finally, the last kind of germ cell tumor comes from placental tissue, and it’s called choriocarcinoma.
These are malignant tumors, which usually arise as a complication of pregnancy, but in rare cases, can occur in the ovaries.
Under the microscope, they contain two types of large cells, cytotrophoblasts with central nuclei and pale cytoplasm, and syncytiotrophoblasts that have multiple nuclei and darker cytoplasm.
Choriocarcinomas look very similar to placental tissue but without villi. They are usually quite small but have a high chance of bleeding and spreading via the circulation.
For your test, remember that lab tests will show extremely elevated hCG levels, which is secreted by syncytiotrophoblasts.

Sex Cord-Stromal12:08–13:17

Now, the alpha subunit of hCG is structurally similar to thyroid-stimulating hormone or TSH for short. So, in very high concentrations, it can stimulate TSH receptors, causing symptoms of hyperthyroidism, like heat intolerance, sweating, palpitations, frequent or loose bowel movements and weight loss.
So if a question describes a female with hyperthyroidism, normal thyroid examination, an ovarian mass, plus very elevated hCG levels, it’s probably a choriocarcinoma of the ovaries.
OKay, moving on! The third big category of ovarian tumors involves sex cord-stromal tumors that originate from the connective tissue of the ovary.
There are four main types: granulosa cell tumors, thecomas, fibromas and Sertoli-Leydig cell tumors.Granulosa cell tumor is the most common malignant stromal tumor.
For your test, it’s important to know that under the microscope, you can see granulosa-like cells randomly arranged around pockets of eosinophilic fluid, and these are called Call-Exner bodies.
Lab tests also show elevated levels of inhibin b, which is a hormone produced by granulosa cells, and serves as a tumor marker.Theca- cell tumors or thecomas are benign tumors composed of theca cells.

Fibromas13:17–13:35

An extremely high-yield fact is that both granulosa- and theca cell-tumors are more common in postmenopausal individuals and can secrete excessive estrogen, so these tumors are associated with signs of estrogen excess like weight gain, breast tenderness, irregular menses, and heavy menstrual bleeding, or menorrhagia.

Sertoli-Leydig Cell Tumo13:35–14:53

Next, fibromas are benign tumors made of bundles of fibroblasts. The important thing to remember is that they are a part of Meigs syndrome which also include ascites, or fluid in the abdomen or peritoneal cavity, and hydrothorax, which is fluid buildup in the chest or pleural cavity.Lastly, Sertoli-Leydig cell tumors are usually benign tumors, composed of Sertoli cells and Leydig cells.
These cells form testicular tubular structures lined by round Sertoli cells and surrounded by a fibrous stroma. Adjacent to the tubules, there are Leydig cells.
And a key piece of information is that Leydig cells contain Reinke crystals, which are pink, rod-like crystals inside their cytoplasm.
Another important thing to remember is that these tumors can be hormonally active, meaning they could secrete androgens like testosterone.
For this reason, they are associated with virilization, and symptoms include acne, hirsutism, deeper voice, and hair loss.
Okay, remember that all these ovarian tumors are primary and the majority only affect one ovary. If a test question mentions bilateral ovarian masses, think of Krukenberg tumor.
Krukenberg tumors are malignancies that come from the gastrointestinal system, most often a metastatic diffuse gastric carcinoma that metastasized to the ovaries.

Risk Factors14:53–16:15

Another high-yield fact to know is that these ovarian tumors are mucin-secreting and have signet ring cells. These are cells with a large vacuole filled with mucin, which resembles the finger hole of a ring and the nucleus is pushed towards the edge like the gemstone on top of the ring .Now, there are plenty of risk factors associated with ovarian cancers, but the most important one you need to remember for your exams is the number of ovulatory cycles.
The fewer ovulatory cycles, the smaller the risk of developing ovarian cancer. This is because ovulation requires continual replication, so the more the cells divide, the more likely they will mutate and become cancerous.
So, never having been pregnant, infertility, early age of menarche, late menopause as well as endometriosis and PCOS, due to the fact that they are both related with infertility, all increase the risk for ovarian cancer.
In contrast, having children, breastfeeding, oral and contraceptive use can decrease the risk due to the inhibition of ovulation.
For your exams, remember that there’s genetic predisposition if BRCA-1 or BRCA-2 mutation is present. Both of these genes are autosomal dominant.
Individuals who have a BRCA1 type mutation have an increased risk of both ovarian and breast cancer. But remember that ovarian cancer is usually the one with the worse prognosis.

Symptoms16:15–18:24

For your exam, a family history of endometrial cancer, colon cancer, or other gastrointestinal cancers can be a hint for an autosomal dominant disorder known as hereditary nonpolyposis colorectal cancer, or Lynch syndrome, where there’s also a higher risk for developing ovarian cancer.Now, many ovarian cysts and tumors are asymptomatic.
When there are symptoms they are typically subtle and may include a change in bowel habits and pelvic discomfort that ranges from a pulling sensation in the groin, fullness or bloating in the pelvis or abdomen, and dull, aching lower abdominal or pelvic pain, especially in the case of large tumors, like cystic teratomas.
Large tumors can even cause ovarian torsion, where the ovary twists around the suspensory ligament. Since this ligament contains the ovarian blood vessels, torsion can cut off the blood supply to the ovary, resulting in sudden, sharp and severe, acute pelvic pain and ovarian ischemia.
Since there are important symptoms associated with each of the disorders we’ve discussed, let’s go over the key ones again.
For polycystic ovary syndrome and Sertoli- Leydig cell tumors, a key clue is amenorrhea, acne, and hirsutism, or excessive hair growth on the chin and upper lip, chest, and back.
Endometriomas can cause dysmenorrhea, or painful menstruation, and are associated with fertility issues. In struma ovarii and some cases of choriocarcinoma, there will be symptoms of hyperthyroidism.
Granulosa or theca cell tumors will lead to signs of estrogen excess. Prior to puberty, this results in precocious puberty, which is when signs of puberty appear before the age of 8 in females.
In reproductive age, it can cause menorrhagia and metrorrhagia. And post-menopause, which is when most granulosa or theca cell tumors present, they can present with endometrial hyperplasia with uterine bleeding.
Now, in more severe cases, symptoms may arise from a malignant tumor metastasizing to other organs. This can present as ascites, abdominal masses, abdominal distension, bowel obstruction, lymph node masses, or pleural effusion.

Diagnosis18:24–19:27

An especially high-yield clue for metastatic ovarian cancer is also a Sister Mary Joseph nodule, which are bumps found around the umbilicus or belly button.
However, it’s extremely important to remember that in most cases, Sister Mary Joseph nodules are associated with gastric cancer.Diagnosis of ovarian cyst or tumor starts with a physical examination, which will include a pelvic examination, a blood test looking for specific tumor markers like LDH, β-hCG, AFP and inhibin b.
Imaging studies should start with a transvaginal or abdominal ultrasound. Ultimately, a biopsy is the only way to get a definitive diagnosis of the type of cyst of tumor.
CT or MRI scanning can then be used to assess if the tumor has spread.Treatment for ovarian cysts varies based on type and size.
Small simple cysts will usually get better on their own, whereas larger, complex cysts should be surgically removed. For ovarian tumors, treatment usually involves chemotherapy, surgery, and sometimes radiotherapy.

Review19:27–20:47

Now, for your exams, it’s important to know that levels of carbohydrate antigen 125, or CA 125, are tumor markers used to monitor response to therapy and potential relapse.
It’s not specific enough to be used for diagnosis or screening. All right, as a quick recap, ovarian cysts can broadly be grouped as simple and complex cysts.
Simple cysts include follicular cysts, luteal cysts, and theca-lutein cysts. Complex cysts frequently occur with ovarian tumors.
The most common type of ovarian tumors are epithelial tumors, which can be serous, mucinous, endometrioid and transitional.
Next, there are germ cell tumors, which include teratomas which can be mature and benign or immature and malignant, dysgerminomas which are malignant and affect adolescents, yolk sac tumors, which are the most common type in children, and choriocarcinomas, which are associated with hyperthyroidism.
Sex cord-stromal tumors include granulosa cell tumors, which are malignant and thecomas which are benign, both are associated with precocious puberty or abnormal vaginal bleeding.
Fibromas are benign and are a part of Meigs syndrome, while Sertoli-Leydig cell tumors, can secrete excess androgens. Finally, bilateral ovarian tumors usually arise from metastatic gastric carcinomas and are known as Krukenberg tumors.

Summary20:47–21:41

Now, risk of ovarian tumors increases with the number of ovulation cycles. Mutations in the BRCA-1 and 2 gene and lynch syndrome are also associated with an increased risk of developing ovarian tumors.
Alright, back to our cases. Rebecca presented with vague symptoms, like abdominal discomfort, bloating, and a change in bowel habits, but she also had a Sister Mary Joseph nodule on physical exam.
These point to a possible ovarian carcinoma. Her ultrasound showed a complex ovarian cyst, which is also characteristic of ovarian cancer.
Other clues include her past history of endometriosis,
Ovarian cysts and tumors: Video, Causes, Symptoms | Osmosis